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RNA-dependent protein kinase (PKR) may have a positive regulatory role in controlling tumor growth and progression in hepatocellular carcinoma (HCC). However, the downstream substrates and the molecular mechanism of PKR in the growth and progression of HCC have not been clarified. In this study, mass spectrometry analysis was performed with immunoprecipitated samples, and 4.1R was identified as a protein that binds to PKR. In transfected COS7 cells, an immunoprecipitation experiment showed that 4.1R binds to wild-type PKR, but not to a kinase-deficient mutant PKR, suggesting that PKR binds to 4.1R in a kinase activity-dependent manner. In HCC cell lines, HuH7 and HepG2, the expression level of 4.1R protein was shown to be regulated by protein expression and activation of PKR. Interestingly, high expression of 4.1R, as well as PKR, is associated with a worse prognosis in HCC. PKR increased HCC cell growth in both anchorage-dependent and anchorage-independent manners, whereas 4.1R was involved in HCC cell growth only in an anchorage-independent manner, not in an anchorage-dependent manner. The rescue experiment indicated that increased anchorage-independent growth of HCC cells by PKR might be caused by 4.1R. In conclusion, PKR associates with 4.1R and promotes anchorage-independent growth of HCC. The PKR-4.1R axis might be a new therapeutic target in HCC. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Fatty acid-binding protein 4 (FABP4) has been reported to act as a hepatic insulin resistance factor. We previously reported that fasting FABP4 was correlated with insulin resistance measurements derived from the glucose clamp, and another study reported that postprandial FABP4 levels were decreased in healthy volunteers but were not reported (or known) in participants with type 2 diabetes. We have limited knowledge about the direct effect of FABP4 on muscle cells. We investigated the postprandial FABP4 levels in participants with type 2 diabetes, and the basic mechanism of muscle insulin resistance and FABP4. Methods: We performed a meal tolerance test and hyperinsulinaemic–euglycaemic clamp in 22 participants with type 2 diabetes and 26 participants without diabetes. We measured fasting and postprandial serum FABP4. We cultured mouse C2C12 muscle cells, and investigated the effect of FABP4 on glucose uptake. We analysed insulin signalling by western blot and insulin binding assay. Results: The postprandial FABP4 level in participants with type 2 diabetes was higher than that in participants without diabetes. Participants without diabetes had lower postprandial FABP4 than fasting except for one participant, whereas one-third of participants with type 2 diabetes had higher postprandial FABP4 than fasting. Postprandial FABP4 was correlated with the muscle insulin resistance M/I value from a glucose clamp in participants without diabetes (r=−0.42, p<0.05). The increase in FABP4 after a meal correlated with the muscle insulin resistance M/I value (r=−0.44, p<0.05) and the difference between fasting and postprandial glucagon in participants with type 2 diabetes (r=0.36, p<0.05). FABP4 alone appears to increase glucose uptake, and the combination of FABP4 and insulin decreases glucose uptake when compared with insulin alone. FABP4 inhibits insulin signalling of muscle cells through decreases in phosphorylation of insulin receptor substrate 1 and Akt. The physiological concentration of FABP4 did not inhibit insulin binding to muscle cells. Conclusions/interpretation: These results suggested that the postprandial FABP4 level is associated with insulin resistance, and FABP4 may suppress insulin signals. [ABSTRACT FROM AUTHOR]

Sweat is an essential protection system for the body, but its failure can result in pathologic conditions, including several skin diseases, such as palmoplantar pustulosis (PPP). As reduced intraepidermal E-cadherin expression in skin lesions was confirmed in PPP skin lesions, a role for interleukin (IL)-1-rich sweat in PPP has been proposed, and IL-1 has been implicated in the altered E-cadherin expression observed in both cultured keratinocytes and mice epidermis. For further investigation, live imaging of sweat perspiration on a mouse toe-pad under two-photon excitation microscopy was performed using a novel fluorescent dye cocktail (which we named JSAC). Finally, intraepidermal vesicle formation which is the main cause of PPP pathogenesis was successfully induced using our "LASER-snipe" technique with JSAC. "LASER-snipe" is a type of laser ablation technique that uses two-photon absorption of fluorescent material to destroy a few acrosyringium cells at a pinpoint location in three-dimensional space of living tissue to cause eccrine sweat leakage. These observatory techniques and this mouse model may be useful not only in live imaging for physiological phenomena in vivo such as PPP pathomechanism investigation, but also for the field of functional physiological morphology. [ABSTRACT FROM AUTHOR]

The definition of the Fresnel wavenumber, which appears in the text, in Section 3.1, is also changed to HT ht Graph Accordingly, the results of the parameter fitting were changed (see Figures 6, 7, 8, and 12b). In our case, the distance between the source and the observer (ground antenna) is relatively short, and the following formula should be used (Yakovlev, [1]): 2 HT ht Graph where HT ht is the distance between the ground antenna and the point of closest approach, and HT ht is the distance between the point of closest approach and the source of radio waves (spacecraft). [Extracted from the article]

Trehalose is the nonreducing disaccharide of glucose, evolutionarily conserved in invertebrates. The living skin equivalent (LSE) is an organotypic coculture containing keratinocytes cultivated on fibroblast-populated dermal substitutes. We demonstrated that human primary fibroblasts treated with highly concentrated trehalose promote significantly extensive spread of the epidermal layer of LSE without any deleterious effects. The RNA-seq analysis of trehalose-treated 2D and 3D fibroblasts at early time points revealed the involvement of the CDKN1A pathway, the knockdown of which significantly suppressed the upregulation of DPT, ANGPT2, VEGFA, EREG, and FGF2. The trehalose-treated fibroblasts were positive for senescence-associated β-galactosidase. Finally, transplantation of the dermal substitute with trehalose-treated fibroblasts accelerated wound closure and increased capillary formation significantly in the experimental mouse wounds in vivo, which was canceled by the CDKN1A knockdown. These data indicate that high-concentration trehalose can induce the senescence-like state in fibroblasts via CDKN1A/p21, which may be therapeutically useful for optimal wound repair.Highly concentrated trehalose induces beneficial senescence-like state in fibroblasts and accelerates the proliferation of keratinocytes and angiogenesis to promote optimal wound repair, demonstrating its therapeutic potential in modulating fibroblast functions. [ABSTRACT FROM AUTHOR]

A detailed analysis of differences in skeletal shape among many individuals is expected to reveal the mechanical significance behind various morphological features. To confirm the distribution of the cortical bone region in cross sections, the relative position of the central mass distribution (CMD) of the cortical bone region to the CMD of the entire cross section was examined. A total of 90 right human femoral skeletons were examined using clinical multi-slice computed tomography. For nine cross sections of each femur, we determined the CMD of the whole area, including both cortical bone and medullary areas, as CMD-W, and that of the cortical bone region in the same cross section as CMD-C, and they were compared. The medial and anterior portion of the cortex was relatively thick just below the lesser trochanter. The posterior cortical bone tended to be relatively thick in the region from the center to the distal part of the diaphysis. Females had a significantly more medially deviated CMD than males throughout the entire diaphysis. These results suggest that femurs with advanced cortical bone thinning tend to have a concentration of cortical bone in their medial portion. CMD-C was located farther from the diaphysis axis as the degree of medial bending increased. Conversely, the greater the lateral bending of the diaphysis, the closer CMD-C was to the diaphysis axis. As the amount of bone decreases with age, self-adjustment could occur so that the cortical bone's critical area remains to prevent a decrease in mechanical strength. [ABSTRACT FROM AUTHOR]

Insulin balls, localized insulin amyloids formed at the site of repeated insulin injections in patients with diabetes, cause poor glycemic control and cytotoxicity. Our previous study has shown that insulin forms two types of amyloids; toxic amyloid formed from the intact insulin ((i)-amyloid) and less-toxic amyloid formed in the presence of the reducing reagent TCEP ((r)-amyloid), suggesting insulin amyloid polymorphism. However, the differences in the formation mechanism and cytotoxicity expression are still unclear. Herein, we demonstrate that the liquid droplets, which are stabilized by electrostatic interactions, appear only in the process of toxic (i)-amyloid formation, but not in the less-toxic (r)-amyloid formation process. The effect of various additives such as arginine, 1,6-hexanediol, and salts on amyloid formation was also examined to investigate interactions that are important for amyloid formation. Our results indicate that the maturation processes of these two amyloids were significantly different, whereas the nucleation by hydrophobic interactions was similar. These results also suggest the difference in the formation mechanism of two different insulin amyloids is attributed to the difference in the intermolecular interactions and could be correlated with the cytotoxicity. [ABSTRACT FROM AUTHOR]

The planetary missions including the Venus Climate Orbiter 'Akatsuki' provide new information on various atmospheric phenomena. Nevertheless, it is difficult to elucidate their three-dimensional structures globally and continuously only from observations because satellite observations are considerably limited in time and space. We constructed the first 'objective analysis' of Venus' atmosphere by assimilating cloud-top horizontal winds on the dayside from the equator to mid-latitudes, which is frequently obtained from Akatsuki's Ultraviolet Imager (UVI). The three-dimensional structures of thermal tides, found recently to play a crucial role in maintaining the super rotation, are greatly improved by the data assimilation. This result is confirmed by comparison with Akatsuki's temperature observations. The momentum transport caused by the thermal tides and other disturbances are also modified by the wind assimilation and agrees well with those estimated from the UVI observations. The assimilated dataset is reliable and will be open to the public along with the Akatsuki observations for further investigation of Venus' atmospheric phenomena. [ABSTRACT FROM AUTHOR]

Cancer relapse after chemotherapy remains a main cause of cancer-related death. Although the relapse is thought to result from the propagation of resident cancer stem cells1, a lack of experimental platforms that enable the prospective analysis of cancer stem cell dynamics with sufficient spatiotemporal resolution has hindered the testing of this hypothesis. Here we develop a live genetic lineage-tracing system that allows the longitudinal tracking of individual cells in xenotransplanted human colorectal cancer organoids, and identify LGR5+ cancer stem cells that exhibit a dormant behaviour in a chemo-naive state. Dormant LGR5+ cells are marked by the expression of p27, and intravital imaging provides direct evidence of the persistence of LGR5+p27+ cells during chemotherapy, followed by clonal expansion. Transcriptome analysis reveals that COL17A1—a cell-adhesion molecule that strengthens hemidesmosomes—is upregulated in dormant LGR5+p27+ cells. Organoids in which COL17A1 is knocked out lose the dormant LGR5+p27+ subpopulation and become sensitive to chemotherapy, which suggests that the cell–matrix interface has a role in the maintenance of dormancy. Chemotherapy disrupts COL17A1 and breaks the dormancy in LGR5+p27+ cells through FAK–YAP activation. Abrogation of YAP signalling prevents chemoresistant cells from exiting dormancy and delays the regrowth of tumours, highlighting the therapeutic potential of YAP inhibition in preventing cancer relapse. These results offer a viable therapeutic approach to overcome the refractoriness of human colorectal cancer to conventional chemotherapy.A genetic lineage-tracing system in human colorectal organoids identifies a population of dormant cancer cells that persists during chemotherapy and enables cancer regrowth, and the cell-adhesion molecule COL17A1 has a key role in the process of breaking dormancy. [ABSTRACT FROM AUTHOR]

Developmental dysplasia of the hip (DDH) is characterized by anatomical abnormalities of the hip joint, ranging from mild acetabular dysplasia to hip subluxation and eventually dislocation. The mechanism underlying the cartilage degeneration of the hip joints exposed to reduced dynamic loads due to hip dislocation remains unknown. We established a rodent hip dislocation (disarticulation; DA) model of DDH (DA-DDH rats and mice) by swaddling. Expression levels of periostin (Postn) and catabolic factors, such as interleukin-6 (IL-6) and matrix metalloproteinase 3 (Mmp3), increased and those of chondrogenic markers decreased in the acetabular cartilage of the DA-DDH models. Postn induced IL-6 and Mmp3 expression in chondrocytes through integrin αVβ3, focal adhesion kinase, Src, and nuclear factor-κB (NF-κB) signaling. The microgravity environment created by a random positioning machine induced Postn expression in chondrocytes through signal transducer and activator of transcription 3 (STAT3) signaling. IL-6 stimulated Postn expression via STAT3 signaling. Furthermore, cartilage degeneration was suppressed in the acetabulum of Postn−/− DA-DDH mice compared with that in the acetabulum of wild type DA-DDH mice. In summary, reduced dynamic loads due to hip dislocation induced acetabular cartilage degeneration via IL-6 and MMP3 through STAT3/periostin/NF-κB signaling in the rodent DA-DDH models. [ABSTRACT FROM AUTHOR]

The properties of the coronal plasma at heliocentric distances of 1.5 – 8.9 R ⊙ (solar radii) were studied with radio-occultation observations using JAXA's Akatsuki spacecraft in 2016. Physical parameters that characterize the solar wind were retrieved from the intensity-scintillation time series by fitting a theoretical spectrum to the observed power spectra. The derived solar-wind velocity clearly shows a difference between the fast wind and the slow wind, which was identified based on IPS observations. The inner scale, at which fluid motions dissipate and kinetic energy is converted to heat, increases with the heliocentric distance, and the fast wind has larger inner scales than the slow wind. By applying wavelet analysis to the frequency time series, we detected quasi-periodic fluctuations in the electron density. The density oscillations are considered to be manifestations of acoustic waves, which were generated from Alfvén waves originating from the photosphere, and the energy fluxes of those acoustic waves were estimated. The relative density-amplitude peaks around 4 – 6 R ⊙ and the wave-energy flux decreases beyond ≈ 6 R ⊙ , implying that the acoustic waves dissipate to heat the corona. The phase-scintillation spectrum that we obtained cannot be expressed by a single power law. A break is seen around the frequency of 0.5 – 2 Hz beyond ≈ 6 R ⊙ , suggesting an excess power other than turbulence at lower frequencies. The enhancement of the relative density amplitude around 6 R ⊙ found by the wavelet analysis might explain this excess power. The acoustic wave-energy flux in the fast solar wind tends to exceed that in the slow wind, suggesting that the fast wind is powered by a larger injection of Alfvén-wave energy than the slow wind. [ABSTRACT FROM AUTHOR]

Sodium–glucose cotransporter 2 inhibitor (SGLT2i) treatment is a therapeutic approach for type 2 diabetes mellitus (T2DM). Some reports have shown that SGLT2i treatment improves insulin resistance; however, few studies have evaluated insulin resistance by the glucose clamp method. Hepatic insulin clearance (HIC) is a new pathophysiological mechanism of T2DM. The effect of SGLT2i treatment on hepatic insulin clearance and insulin resistance is not well known. We investigated the effect of SGLT2i treatment on insulin resistance, insulin secretion, incretin levels, body composition, and hepatic insulin clearance. We conducted a meal tolerance test (MTT) and a hyperinsulinemic-euglycemic clamp test in 9 T2DM patients. Ipragliflozin (50 mg/day) was administered, and the MTT and clamp test were performed after 4 months. We calculated HIC as the postprandial C-peptide AUC-to-insulin AUC ratio. We also measured GLP-1, GIP, and glucagon levels during the MTT. Body weight and HbA1c were decreased, although not significantly, after 4 months of treatment. Postprandial glucose, fasting insulin and postprandial insulin were significantly decreased. Insulin resistance with the glucose clamp was not changed, but the HOMA-IR and insulin sensitivity indices were significantly improved. Incretin and glucagon levels were not changed. Hepatic insulin clearance was significantly increased, but whole-body insulin clearance was not changed. The FIB-4 index and fatty liver index were significantly reduced. The HOMA-beta and insulinogenic indices were not changed, but the C-peptide index was significantly increased. Although the number of patients was small, these results suggested that SGLT2i treatment improved liver function, decreased hepatic insulin resistance, and increased hepatic insulin clearance, despite the small weight reduction. [ABSTRACT FROM AUTHOR]

Martian moons exploration, MMX, is the new sample return mission planned by the Japan Aerospace Exploration Agency (JAXA) targeting the two Martian moons with the scheduled launch in 2024 and return to the Earth in 2029. The major scientific objectives of this mission are to determine the origin of Phobos and Deimos, to elucidate the early Solar System evolution in terms of volatile delivery across the snow line to the terrestrial planets having habitable surface environments, and to explore the evolutionary processes of both moons and Mars surface environment. To achieve these objectives, during a stay in circum-Martian space over about 3 years MMX will collect samples from Phobos along with close-up observations of this inner moon and carry out multiple flybys of Deimos to make comparative observations of this outer moon. Simultaneously, successive observations of the Martian atmosphere will also be made by utilizing the advantage of quasi-equatorial spacecraft orbits along the moons' orbits. [ABSTRACT FROM AUTHOR]

Japan Aerospace Exploration Agency (JAXA) plans a Phobos sample return mission (MMX: Martian Moons eXploration). In this study, we review the related works on the past climate of Mars, its evolution, and the present climate and weather to describe the scientific goals and strategies of the MMX mission regarding the evolution of the Martian surface environment. The MMX spacecraft will retrieve and return a sample of Phobos regolith back to Earth in 2029. Mars ejecta are expected to be accumulated on the surface of Phobos without being much shocked. Samples from Phobos probably contain all types of Martian rock from sedimentary to igneous covering all geological eras if ejecta from Mars could be accumulated on the Phobos surface. Therefore, the history of the surface environment of Mars can be restored by analyzing the returned samples. Remote sensing of the Martian atmosphere and monitoring ions escaping to space while the spacecraft is orbiting Mars in the equatorial orbit are also planned. The camera with multi-wavelength filters and the infrared spectrometer onboard the spacecraft can monitor rapid transport processes of water vapor, dust, ice clouds, and other species, which could not be traced by the previous satellites on the sun-synchronous polar orbit. Such time-resolved pictures of the atmospheric phenomena should be an important clue to understand both the processes of water exchange between the surface/underground reservoirs and the atmosphere and the drivers of efficient material transport to the upper atmosphere. The mass spectrometer with unprecedented mass resolution can observe ions escaping to space and monitor the atmospheric escape which has made the past Mars to evolve towards the cold and dry surface environment we know today. Together with the above two instruments, it can potentially reveal what kinds of atmospheric events can transport tracers (e.g., H2O) upward and enhance the atmospheric escape. [ABSTRACT FROM AUTHOR]

Despite the high sensitivity of renal cell carcinoma (RCC) to immunotherapy, RCC has been recognized as an unusual disease in which CD8+ T-cell infiltration into the tumor beds is related to a poor prognosis. To approach the inner landscape of immunobiology of RCC, we performed multiplexed seven-color immunohistochemistry (CD8, CD39, PD-1, Foxp3, PD-L1, and pan-cytokeratin AE1/AE3 with DAPI), which revealed the automated single-cell counts and calculations of individual cell-to-cell distances. In total, 186 subjects were included, in which CD39 was used as a marker for distinguishing tumor-specific (CD39+) and bystander (CD39−) T-cells. Our clear cell RCC cohort also revealed a poor prognosis if the tumor showed increased CD8+ T-cell infiltration. Intratumoral CD8+CD39+ T-cells as well as their exhausted CD8+CD39+PD-1+ T-cells in the central tumor areas enabled the subgrouping of patients according to malignancy. Analysis using specimens post-antiangiogenic treatment revealed a dramatic increase in proliferative Treg fraction Foxp3+PD-1+ cells, suggesting a potential mechanism of hyperprogressive disease after uses of anti-PD-1 antibody. Our cell-by-cell study platform provided spatial information on tumors, where bystander CD8+CD39− T-cells were dominant in the invasive margin areas. We uncovered a potential interaction between CD8+CD39+PD-1+ T-cells and Foxp3+PD-1+ Treg cells due to cell-to-cell proximity, forming a spatial niche more specialized in immunosuppression under PD-1 blockade. A paradigm shift to the immunosuppressive environment was more obvious in metastatic lesions; rather the infiltration of Foxp3+ and Foxp3+PD-1+ Treg cells was more pronounced. With this multiplexed single-cell pathology technique, we revealed further insight into the immunobiological standing of RCC. [ABSTRACT FROM AUTHOR]

Although Venus is a terrestrial planet similar to Earth, its atmospheric circulation is much different and poorly characterized1. Winds at the cloud top have been measured predominantly on the dayside. Prominent poleward drifts have been observed with dayside cloud tracking and interpreted to be caused by thermal tides and a Hadley circulation2–4; however, the lack of nightside measurements over broad latitudes has prevented the unambiguous characterization of these components. Here we obtain cloud-tracked winds at all local times using thermal infrared images taken by the Venus orbiter Akatsuki, which is sensitive to an altitude of about 65 kilometres5. Prominent equatorward flows are found on the nightside, resulting in null meridional velocities when these are zonally averaged. The velocity structure of the thermal tides was determined without the influence of the Hadley circulation. The semidiurnal tide was found to have an amplitude large enough to contribute to the maintenance of the atmospheric superrotation. The weakness of the mean meridional flow at the cloud top implies that the poleward branch of the Hadley circulation exists above the cloud top and that the equatorward branch exists in the clouds. Our results should shed light on atmospheric superrotation in other celestial bodies.Cloud-top thermal images obtained by the Akatsuki orbiter show that Venus has almost null mean meridional circulation at the cloud top, because poleward circulation on the dayside is offset by equatorward circulation on the nightside. [ABSTRACT FROM AUTHOR]

Two-photon excitation can lower phototoxicity and improve penetration depth, but its narrow excitation range restricts its applications in light-sheet microscopy. Here, we propose simple illumination optics, a lens-axicon triplet composed of an axicon and two convex lenses, to generate longer extent Bessel beams. This unit can stretch the beam full width at half maximum of 600–1000 μm with less than a 4-μm waist when using a 10× illumination lens. A two-photon excitation digital scanned light-sheet microscope possessing this range of field of view and ~2–3-μm axial resolution is constructed and used to analyze the cellular dynamics over the whole body of medaka fish. We demonstrate long-term time-lapse observations over several days and high-speed recording with ~3 mm3 volume per 4 s of the embryos. Our system is minimal and suppresses laser power loss, which can broaden applications of two-photon excitation in light-sheet microscopy. Here, the authors present a two-photon light-sheet microscopy with an extended Bessel beam for a tunable field of view and reduced photodamage. They demonstrate long-term imaging of cellular dynamics over the whole body of medaka fish. [ABSTRACT FROM AUTHOR]

MYOD-induced microRNA-494-3p expression inhibits fast oxidative myotube formation by downregulating myosin heavy chain 2 (MYH2) in human induced pluripotent stem cells (hiPSCs) during skeletal myogenesis. However, the molecular mechanisms regulating MYH2 expression via miR-494-3p remain unknown. Here, using bioinformatic analyses, we show that miR-494-3p potentially targets the transcript of the E1A-binding protein p300 at its 3′-untranslated region (UTR). Myogenesis in hiPSCs with the Tet/ON-myogenic differentiation 1 (MYOD1) gene (MyoD-hiPSCs) was induced by culturing them in doxycycline-supplemented differentiation medium for 7 days. p300 protein expression decreased after transient induction of miR-494-3p during myogenesis. miR-494-3p mimics decreased the levels of p300 and its downstream targets MYOD and MYH2 and myotube formation efficiency. p300 knockdown decreased myotube formation efficiency, MYH2 expression, and basal oxygen consumption rate. The binding of miR-494-3p to the wild type p300 3′-UTR, but not the mutated site, was confirmed using luciferase assay. Overexpression of p300 rescued the miR-494-3p mimic-induced phenotype in MyoD-hiPSCs. Moreover, miR-494-3p mimic reduced the levels of p300, MYOD, and MYH2 in skeletal muscles in mice. Thus, miR-494-3p might modulate MYH2 expression and fast oxidative myotube formation by directly regulating p300 levels during skeletal myogenesis in MyoD-hiPSCs and murine skeletal muscle tissues. [ABSTRACT FROM AUTHOR]

Transforming growth factor-β (TGF-β) and bone morphogenetic protein (BMP) play important roles in bone metabolism. Smad ubiquitination regulatory factors (Smurfs) regulate TGF-β/BMP signaling via ubiquitination, resulting in degradation of signaling molecules to prevent excessive activation of TGF-β/BMP signaling. Though Smurf2 has been shown to negatively regulate TGF-β/Smad signaling, its involvement in BMP/Smad signaling in bone metabolism has not been thoroughly investigated. In the present study, we sought to evaluate the role of Smurf2 in BMP/Smad signaling in bone metabolism. Absorbable collagen sponges containing 3 μg of recombinant human BMP2 (rhBMP2) were implanted in the dorsal muscle pouches of wild type (WT) and Smurf2−/− mice. The rhBMP2-induced ectopic bone in Smurf2−/− mice showed greater bone mass, higher mineral apposition and bone formation rates, and greater osteoblast numbers than the ectopic bone in WT mice. In WT mice, the ectopic bone consisted of a thin discontinuous outer cortical shell and scant inner trabecular bone. In contrast, in Smurf2−/− mice, the induced bone consisted of a thick, continuous outer cortical shell and abundant inner trabecular bone. Additionally, rhBMP2-stimulated bone marrow stromal cells (BMSCs) from Smurf2−/− mice showed increased osteogenic differentiation. Smurf2 induced the ubiquitination of Smad1/5. BMP/Smad signaling was enhanced in Smurf2−/− BMSCs stimulated with rhBMP2, and the inhibition of BMP/Smad signaling suppressed osteogenic differentiation of these BMSCs. These findings demonstrate that Smurf2 negatively regulates BMP/Smad signaling, thereby identifying a new regulatory mechanism in bone metabolism. [ABSTRACT FROM AUTHOR]

Superrotation is a dynamical regime where the atmosphere circulates around the planet in the direction of planetary rotation with excess angular momentum in the equatorial region. Superrotation is known to exist in the atmospheres of Venus, Titan, Jupiter, and Saturn in the solar system. Some of the exoplanets also exhibit superrotation. Our understanding of superrotation in a framework of circulation regimes of the atmospheres of terrestrial planets is in progress thanks to the development of numerical models; a global instability involving planetary-scale waves seems to play a key role, and the dynamical state depends on the Rossby number, a measure of the relative importance of the inertial and Coriolis forces, and the thermal inertia of the atmosphere. Recent general circulation models of Venus's and Titan's atmospheres demonstrated the importance of horizontal waves in the angular momentum transport in these atmospheres and also an additional contribution of thermal tides in Venus's atmosphere. The atmospheres of Jupiter and Saturn also exhibit strong superrotation. Recent gravity data suggests that these superrotational flows extend deep into the planet, yet currently no single mechanism has been identified as driving this superrotation. Moreover, atmospheric circulation models of tidally locked, strongly irradiated exoplanets have long predicted the existence of equatorial superrotation in their atmospheres, which has been attributed to the result of the strong day-night thermal forcing. As predicted, recent Doppler observations and infrared phase curves of hot Jupiters appear to confirm the presence of superrotation on these objects. [ABSTRACT FROM AUTHOR]

Carbonaceous (C-type) asteroids1 are relics of the early Solar System that have preserved primitive materials since their formation approximately 4.6 billion years ago. They are probably analogues of carbonaceous chondrites2,3 and are essential for understanding planetary formation processes. However, their physical properties remain poorly known because carbonaceous chondrite meteoroids tend not to survive entry to Earth's atmosphere. Here we report on global one-rotation thermographic images of the C-type asteroid 162173 Ryugu, taken by the thermal infrared imager (TIR)4 onboard the spacecraft Hayabusa25, indicating that the asteroid's boulders and their surroundings have similar temperatures, with a derived thermal inertia of about 300 J m−2 s−0.5 K−1 (300 tiu). Contrary to predictions that the surface consists of regolith and dense boulders, this low thermal inertia suggests that the boulders are more porous than typical carbonaceous chondrites6 and that their surroundings are covered with porous fragments more than 10 centimetres in diameter. Close-up thermal images confirm the presence of such porous fragments and the flat diurnal temperature profiles suggest a strong surface roughness effect7,8. We also observed in the close-up thermal images boulders that are colder during the day, with thermal inertia exceeding 600 tiu, corresponding to dense boulders similar to typical carbonaceous chondrites6. These results constrain the formation history of Ryugu: the asteroid must be a rubble pile formed from impact fragments of a parent body with microporosity9 of approximately 30 to 50 per cent that experienced a low degree of consolidation. The dense boulders might have originated from the consolidated innermost region or they may have an exogenic origin. This high-porosity asteroid may link cosmic fluffy dust to dense celestial bodies10. Thermal imaging data obtained from the spacecraft Hayabusa2 reveal that the carbonaceous asteroid 162173 Ryugu is an object of unusually high porosity. [ABSTRACT FROM AUTHOR]

The therapeutic effects of C16, which is an inhibitor of RNA-dependent protein kinase (PKR), on growth of hepatocellular carcinoma (HCC) cells and tumor progression in vitro and in vivo were evaluated. Huh7 cells, a human HCC cell line, were used. The effects of C16 on cell viability were evaluated with the MTT assay, and real-time RT-PCR was performed. Huh7 cells were grafted into immunodeficient mice, and the in vivo effects of C16 on tumorigenesis were examined. C16 suppressed proliferation of HCC cells in a dose-dependent manner in vitro. Mouse models with xenograft transplantation showed that the inhibitor suppressed the growth of HCC cells in vivo. Moreover, C16 decreased angiogenesis in HCC tissue in the xenograft model. Consistent with these results in mice, transcript levels of vascular endothelial growth factor-A and factor-B, platelet-derived growth factor-A and factor-B, fibroblast growth factor-2, epidermal growth factor, and hepatocyte growth factor, which are angiogenesis-related growth factors, were significantly decreased by C16 in vitro. In conclusion, the PKR inhibitor C16 blocked tumor cell growth and angiogenesis via a decrease in mRNA levels of several growth factors. C16 may be useful in the treatment of HCC. [ABSTRACT FROM AUTHOR]

Venus is covered with thick clouds. Ultraviolet (UV) images at 0.3-0.4 microns show detailed cloud features at the cloud-top level at about 70 km, which are created by an unknown UV-absorbing substance. Images acquired in this wavelength range have traditionally been used to measure winds at the cloud top. In this study, we report low-latitude winds obtained from the images taken by the UV imager, UVI, onboard the Akatsuki orbiter from December 2015 to March 2017. UVI provides images with two filters centered at 365 and 283 nm. While the 365-nm images enable continuation of traditional Venus observations, the 283-nm images visualize cloud features at an SO absorption band, which is novel. We used a sophisticated automated cloud-tracking method and thorough quality control to estimate winds with high precision. Horizontal winds obtained from the 283-nm images are generally similar to those from the 365-nm images, but in many cases, westward winds from the former are faster than the latter by a few m/s. From previous studies, one can argue that the 283-nm images likely reflect cloud features at higher altitude than the 365-nm images. If this is the case, the superrotation of the Venusian atmosphere generally increases with height at the cloud-top level, where it has been thought to roughly peak. The mean winds obtained from the 365-nm images exhibit local time dependence consistent with known tidal features. Mean zonal winds exhibit asymmetry with respect to the equator in the latter half of the analysis period, significantly at 365 nm and weakly at 283 nm. This contrast indicates that the relative altitude may vary with time and latitude, and so are the observed altitudes. In contrast, mean meridional winds do not exhibit much long-term variability. A previous study suggested that the geographic distribution of temporal mean zonal winds obtained from UV images from the Venus Express orbiter during 2006-2012 can be interpreted as forced by topographically induced stationary gravity waves. However, the geographic distribution of temporal mean zonal winds we obtained is not consistent with that distribution, which suggests that the distribution may not be persistent. [ABSTRACT FROM AUTHOR]

The status and initial products of the 1-μm camera onboard the Akatsuki mission to Venus are presented. After the successful retrial of Venus' orbit insertion on Dec. 2015 (5 years after the failure in Dec. 2010), and after a long cruise under intense radiation, damage in the detector seems small and fortunately insignificant in the final quality of the images. More than 600 dayside images have been obtained since the beginning of regular operation on Apr. 2016 although nightside images are less numerous (about 150 in total at three wavelengths) due to the light scattered from the bright dayside. However, data acquisition stopped after December 07, 2016, due to malfunction of the electronics and has not been resumed since then. The 0.90-µm dayside images are of sufficient quality for the cloud-tracking procedure to retrieve wind field in the cloud region. The results appear to be similar to those reported by previous 1-μm imaging by Galileo and Venus Express. The representative altitude sampled for such dayside images is estimated to be 51-55 km. Also, the quality of the nightside 1.01-µm images is sufficient for a search for active volcanism, since interference due to cloud inhomogeneity appears to be insignificant. The quality of the 0.97-µm images may be insufficient to achieve the expected spatial resolution for the near-surface HO mixing ratio retrievals. [ABSTRACT FROM AUTHOR]

We provide an overview of data products from observations by the Japanese Venus Climate Orbiter, Akatsuki, and describe the definition and content of each data-processing level. Levels 1 and 2 consist of non-calibrated and calibrated radiance (or brightness temperature), respectively, as well as geometry information (e.g., illumination angles). Level 3 data are global-grid data in the regular longitude-latitude coordinate system, produced from the contents of Level 2. Non-negligible errors in navigational data and instrumental alignment can result in serious errors in the geometry calculations. Such errors cause mismapping of the data and lead to inconsistencies between radiances and illumination angles, along with errors in cloud-motion vectors. Thus, we carefully correct the boresight pointing of each camera by fitting an ellipse to the observed Venusian limb to provide improved longitude-latitude maps for Level 3 products, if possible. The accuracy of the pointing correction is also estimated statistically by simulating observed limb distributions. The results show that our algorithm successfully corrects instrumental pointing and will enable a variety of studies on the Venusian atmosphere using Akatsuki data. [ABSTRACT FROM AUTHOR]

We review our current knowledge of the atmospheric dynamics of Venus prior to the Akatsuki mission, in the altitude range from the surface to approximately the cloud tops located at about 100 km altitude. The three-dimensional structure of the wind field in this region has been determined with a variety of techniques over a broad range of spatial and temporal scales (from the mesoscale to planetary, from days to years, in daytime and nighttime), spanning a period of about 50 years (from the 1960s to the present). The global panorama is that the mean atmospheric motions are essentially zonal, dominated by the so-called super-rotation (an atmospheric rotation that is 60 to 80 times faster than that of the planetary body). The zonal winds blow westward (in the same direction as the planet rotation) with a nearly constant speed of $\sim 100~\mathrm{m}\, \mathrm{s}^{-1}$ at the cloud tops (65-70 km altitude) from latitude 50°N to 50°S, then decreasing their speeds monotonically from these latitudes toward the poles. Vertically, the zonal winds decrease with decreasing altitude towards velocities $\sim 1\text{--}3~\mathrm{m}\,\mathrm{s}^{-1}$ in a layer of thickness $\sim 10~\text{km}$ close to the surface. Meridional motions with peak speeds of $\sim 15~\mathrm{m}\,\mathrm{s}^{-1}$ occur within the upper cloud at 65 km altitude and are related to a Hadley cell circulation and to the solar thermal tide. Vertical motions with speeds $\sim1\text{--}3~\mathrm{m}\, \mathrm{s}^{-1}$ occur in the statically unstable layer between altitudes of $\sim 50 \text{--} 55~\text{km}$ . All these motions are permanent with speed variations of the order of $\sim10\%$ . Various types of wave, from mesoscale gravity waves to Rossby-Kelvin planetary scale waves, have been detected at and above cloud heights, and are considered to be candidates as agents for carrying momentum that drives the super-rotation, although numerical models do not fully reproduce all the observed features. Momentum transport by atmospheric waves and the solar tide is thought to be an indispensable component of the general circulation of the Venus atmosphere. Another conspicuous feature of the atmospheric circulation is the presence of polar vortices. These are present in both hemispheres and are regions of warmer and lower clouds, seen prominently at infrared wavelengths, showing a highly variable morphology and motions. The vortices spin with a period of 2-3 days. The South polar vortex rotates around a geographical point which is itself displaced from the true pole of rotation by $\sim 3$ degrees. The polar vortex is surrounded and constrained by the cold collar, an infrared-dark region of lower temperatures. We still lack detailed models of the mechanisms underlying the dynamics of these features and how they couple (or not) to the super-rotation. The nature of the super-rotation relates to the angular momentum stored in the atmosphere and how it is transported between the tropics and higher latitudes, and between the deep atmosphere and upper levels. The role of eddy processes is crucial, but likely involves the complex interaction of a variety of different types of eddy, either forced directly by radiative heating and mechanical interactions with the surface or through various forms of instability. Numerical models have achieved some significant recent success in capturing some aspects of the observed super-rotation, consistent with the scenario discussed by Gierasch (J. Atmos. Sci. 32:1038-1044, 1975) and Rossow and Williams (J. Atmos. Sci. 36:377-389, 1979), but many uncertainties remain, especially in the deep atmosphere. The theoretical framework developed to explain the circulation in Venus's atmosphere is reviewed, as well as the numerical models that have been built to elucidate the super-rotation mechanism. These tools are used to analyze the respective roles of the different waves in the processes driving the observed motions. Their limitations and suggested directions for improvements are discussed. [ABSTRACT FROM AUTHOR]

The first year (December 2015 to November 2016) of IR2 after Akatsuki's successful insertion to an elongated elliptical orbit around Venus is reported with performance evaluation and results of data acquisition. The single-stage Stirling-cycle cryo-cooler of IR2 has been operated with various driving voltages to achieve the best possible cooling under the given thermal environment. A total of 3091 images of Venus (1420 dayside images at 2.02 μm and 1671 night-side images at 1.735, 2.26, and 2.32 μm) were acquired in this period. Additionally, 159 images, including images of stars for calibration and dark images for the evaluation of noise levels, were captured. Low-frequency flat images (not available in pre-launch calibration data) have been constructed using the images of Venus acquired from near the pericenter to establish the procedure to correct for the IR2 flat-field response. It was noticed that multiple reflections of infrared light in the PtSi detector caused a weak but extended tail of the point-spread function (PSF), contaminating the night-side disk of Venus with light from the much brighter dayside crescent. This necessitated the construction of an empirical PSF to remove this contamination and also to improve the dayside data by deconvolution, and this work is also discussed. Detailed astrometry is performed on star-field images in the H-band (1.65 μm), hereby confirming that the geometrical distortion of IR2 images is negligible. [ABSTRACT FROM AUTHOR]

After the arrival of Akatsuki spacecraft of Japan Aerospace Exploration Agency at Venus in December 2015, the radio occultation experiment, termed RS (Radio Science), obtained 19 vertical profiles of the Venusian atmosphere by April 2017. An onboard ultra-stable oscillator is used to generate stable X-band downlink signals needed for the experiment. The quantities to be retrieved are the atmospheric pressure, the temperature, the sulfuric acid vapor mixing ratio, and the electron density. Temperature profiles were successfully obtained down to ~ 38 km altitude and show distinct atmospheric structures depending on the altitude. The overall structure is close to the previous observations, suggesting a remarkable stability of the thermal structure. Local time-dependent features are seen within and above the clouds, which is located around 48-70 km altitude. The HSO vapor density roughly follows the saturation curve at cloud heights, suggesting equilibrium with cloud particles. The ionospheric electron density profiles are also successfully retrieved, showing distinct local time dependence. Akatsuki RS mainly probes the low and middle latitude regions thanks to the near-equatorial orbit in contrast to the previous radio occultation experiments using polar orbiters. Studies based on combined analyses of RS and optical imaging data are ongoing. [ABSTRACT FROM AUTHOR]

The Venus Climate Orbiter Akatsuki arrived at Venus in December 2015, and the Longwave Infrared Camera (LIR) onboard the spacecraft started making observations. LIR has acquired more than 8000 images during the first two Venusian years since orbit insertion without any serious faults. However, brightness temperature derived from LIR images contained an unexpected bias that related not to natural phenomena but to a thermal condition of the instrument. The bias could be partially eliminated by keeping the power supply unit for LIR always active, while the residual bias was simply correlated with the baffle temperature. Therefore, deep-space images were acquired at different baffle temperatures on orbit, and a reference table for eliminating the bias from images was prepared. In the corrected images, the brightness temperature was ~ 230 K at the center of the Venus disk, where the effect of limb darkening is negligible. The result is independent of the baffle temperature and consistent with the results of previous studies. Later, a laboratory experiment with the proto model of LIR showed that when the germanium (Ge) lens was heated, its actual temperature was slightly higher than the temperature measured by a thermal sensor attached to the lens holder. The experiment confirmed that transitory baffle heating accounted for the background bias found in the brightness temperature observed by LIR. [ABSTRACT FROM AUTHOR]

The purpose of this study was to clarify the relevance of degenerative changes in the sacroiliac joint (SIJ) and the joints in the lower limb and lumbar spine using age estimation methods. We also examined the shape of the auricular surface to determine the effect of degenerative changes on each joint. A total of 200 iliac auricular surfaces from 100 Japanese male skeletons were examined macroscopically in accordance with conventional methods of age estimation. From the obtained estimated age, we calculated the deflection values, which represented the degree of degenerative changes of the joints. For comparison, we used osteophyte score data of the hip, knee, and zygapophyseal joints in lumbar spines from previous studies which had used the same bone specimens. As a quantitative indicator of auricular surface morphology, we defined the constriction ratio (CR) of the auricular surface and compared the CR values obtained with various measured values. Degenerative changes in the SIJ were positively correlated with those in both the hip joint and zygapophyseal joint, but a correlation with knee joints was found only on the left side. In skeletons from individuals aged ≥60 years as time of death, the CR was significantly different between the group with high scores and those with low scores in both the hip and sacroiliac joints. It has been suggested that degenerative changes in SIJs interact with those in the hip joint and zygapophyseal joint. In addition, the shape of the auricular surface may also be a relevant factor for degenerative changes in these joints. [ABSTRACT FROM AUTHOR]

The thermal infrared imager TIR onboard Hayabusa2 has been developed to investigate thermo-physical properties of C-type, near-Earth asteroid 162173 Ryugu. TIR is one of the remote science instruments on Hayabusa2 designed to understand the nature of a volatile-rich solar system small body, but it also has significant mission objectives to provide information on surface physical properties and conditions for sampling site selection as well as the assessment of safe landing operations. TIR is based on a two-dimensional uncooled micro-bolometer array inherited from the Longwave Infrared Camera LIR on Akatsuki (Fukuhara et al., 2011). TIR takes images of thermal infrared emission in 8 to 12 μm with a field of view of $16 \times 12^{\circ}$ and a spatial resolution of $0.05^{\circ}$ per pixel. TIR covers the temperature range from 150 to 460 K, including the well calibrated range from 230 to 420 K. Temperature accuracy is within 2 K or better for summed images, and the relative accuracy or noise equivalent temperature difference (NETD) at each of pixels is 0.4 K or lower for the well-calibrated temperature range. TIR takes a couple of images with shutter open and closed, the corresponding dark frame, and provides a true thermal image by dark frame subtraction. Data processing involves summation of multiple images, image processing including the StarPixel compression (Hihara et al., 2014), and transfer to the data recorder in the spacecraft digital electronics (DE). We report the scientific and mission objectives of TIR, the requirements and constraints for the instrument specifications, the designed instrumentation and the pre-flight and in-flight performances of TIR, as well as its observation plan during the Hayabusa2 mission. [ABSTRACT FROM AUTHOR]

AKATSUKI is the Japanese Venus Climate Orbiter that was designed to investigate the climate system of Venus. The orbiter was launched on May 21, 2010, and it reached Venus on December 7, 2010. Thrust was applied by the orbital maneuver engine in an attempt to put AKATSUKI into a westward equatorial orbit around Venus with a 30-h orbital period. However, this operation failed because of a malfunction in the propulsion system. After this failure, the spacecraft orbited the Sun for 5 years. On December 7, 2015, AKATSUKI once again approached Venus and the Venus orbit insertion was successful, whereby a westward equatorial orbit with apoapsis of ~440,000 km and orbital period of 14 days was initiated. Now that AKATSUKI's long journey to Venus has ended, it will provide scientific data on the Venusian climate system for two or more years. For the purpose of both decreasing the apoapsis altitude and avoiding a long eclipse during the orbit, a trim maneuver was performed at the first periapsis. The apoapsis altitude is now ~360,000 km with a periapsis altitude of 1000-8000 km, and the period is 10 days and 12 h. In this paper, we describe the details of the Venus orbit insertion-revenge 1 (VOI-R1) and the new orbit, the expected scientific information to be obtained at this orbit, and the Venus images captured by the onboard 1-µm infrared camera, ultraviolet imager, and long-wave infrared camera 2 h after the successful initiation of the VOI-R1. [ABSTRACT FROM AUTHOR]

IR2, a near-infrared camera in the 2-μm region onboard Akatsuki has been developed to primarily study the middle-to-lower atmospheric dynamics of Venus as probed in the 1.74- and 2.3-μm 'windows' of the $$\hbox {CO}_2$$ atmosphere on the night side. The spatial and temporal variability of CO below the clouds is also studied by differentiating 2.32-μm CO-band images from simultaneous 2.26-μm images. Images of the night-side disk in these wavelengths will enable us to determine the zonal and meridional winds near the cloud-base altitudes. IR2 also images at 2.02 μm, the center of a $$\hbox {CO}_2$$ absorption band. Such images can visualize the variation of the cloud-top altitudes as contrast features due to different absorption path lengths of the reflected sunlight. Tracking of the 2.02-μm features will also enable us to obtain wind information at the cloud-top level. Together with the other cameras and the radio science equipment on Akatsuki, IR2 will contribute to understanding of the production and maintenance mechanism of super-rotation in the Venusian atmosphere. During cruise, IR2 observed zodiacal light with a broad-band H filter (1.65 μm), imaged the Earth-moon remotely from a distance of ~30 million km, and determined Venus's phase curves at small phase angles. We have just started the early phase operation check of IR2 at Venus, as the orbit insertion in December 2015 was successful. [ABSTRACT FROM AUTHOR]

Nitrate tolerance is an important problem in the treatment of ischemic heart diseases. The present study investigated whether or not a soluble guanylyl cyclase (sGC) activator can be used as a coronary vasodilator under nitrate-tolerant conditions. Helically cut strips of endothelium-denuded monkey and canine coronary arteries were suspended in organ chambers for isometric tension recording. Nitrate tolerance was induced by a 1-h treatment with nitroglycerin (0.1 mM) followed by 1-h washout of the agent. Control strips were not exposed previously to nitroglycerin, but otherwise were treated identically. The relaxant response to nitroglycerin was dramatically impaired by previous exposure to the drug for 1 h in either monkey or canine coronary arteries, indicating the development of nitrate tolerance. In contrast, development of nitrate tolerance did not affect the relaxant potency and efficacy of the sGC activator BAY 60-2770 in either the monkey or canine coronary arteries. These findings suggest that it may be possible to use sGC activators as substitute drugs for nitroglycerin if tolerance is developed during the treatment of ischemic heart diseases. [ABSTRACT FROM AUTHOR]

In clinical settings, serum antibody levels serve as markers of pathology. For example, antibodies related to autoimmune diseases are among the conventional targets in laboratory tests. Simple clinical tests can improve the efficacy of laboratory practice. This study describes a single-step, wash-free technique for optically detecting antibodies in human serum through the localized surface plasmon resonance (LSPR) of gold nanoparticles. As a proof-of-concept experiment, the amount of antibiotin dissolved in human serum was measured with a LSPR-based biosensor in a wash-free manner using a conventional 96-well microtiter plate and a plate reader. For an efficient surface modification of biosensors, zwitterionic copolymer was used as a scaffold on the gold nanoparticle surface to immobilize antigen and blocking reagent. Single-step, wash-free measurement of antibiotin in human serum was successfully achieved. In addition, nonspecific responses from serum contents were significantly reduced because both the copolymer and hydrophilic antigen reagent that we employed were composed of poly(ethylene oxide) spacer. Comparative experiments of the antigen-antibody reaction in serum to that in buffered solution revealed that serum is a favorable environment for the biological reaction. In conclusion, our gold-nanoparticle-based LSPR method may provide a rapid and simple way to measure the amount of antibody in serum quantitatively in clinical practice. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

The phenomenon of secondary recrystallization in 3 pct Si-Fe electrical steel subjected to relatively high cold rolling reduction rates has been investigated. The texture of the secondary recrystallized sample that has a cold rolling reduction rate of 97.2 pct consists mainly of {110}〈112〉 component, which is quite different from the ideal Goss ({110}〈001〉) texture obtained after lower cold rolling reduction rates. The grain boundary character distribution (GBCD) analysis on the primary recrystallized sample with a cold rolling reduction rate of 97.2 pct indicates that the {110}〈112〉 component has the highest frequency of high energy (HE) boundary with a misorientation angle between 20 and 45 deg, whereas the Goss component in the sample subjected to lower cold rolling reduction rates has the highest frequency of HE boundary. These results indicate that the component with the highest frequency of HE boundary surrounding it after primary recrystallization has the privilege to outgrow other components during secondary recrystallization. However, the GBCD analysis for coincidence site lattice (CSL) boundary points out that the Goss component has the highest frequency of CSL boundaries in the primary recrystallized texture irrespective of the cold rolling reduction applied. These results suggest that the HE model can predict the orientation relationship between the primary and secondary recrystallized textures better than the CSL model. [ABSTRACT FROM AUTHOR]

The European Venus Explorer (EVE) mission described in this paper was proposed in December 2010 to ESA as an 'M-class' mission under the Cosmic Vision programme. It consists of a single balloon platform floating in the middle of the main convective cloud layer of Venus at an altitude of 55 km, where temperatures and pressures are benign (∼25°C and ∼0.5 bar). The balloon float lifetime would be at least 10 Earth days, long enough to guarantee at least one full circumnavigation of the planet. This offers an ideal platform for the two main science goals of the mission: study of the current climate through detailed characterization of cloud-level atmosphere, and investigation of the formation and evolution of Venus, through careful measurement of noble gas isotopic abundances. These investigations would provide key data for comparative planetology of terrestrial planets in our solar system and beyond. [ABSTRACT FROM AUTHOR]

Transforming growth factor-β (TGF-β) ligand is a multifunctional growth factor that regulates various cell behavior, such as cell proliferation, differentiation, migration, and apoptosis. Because TGF-β is a potent growth inhibitor, abnormalities in TGF-β signaling result in carcinogenesis. In addition to tumor suppressor function, TGF-β acts as an oncogenic factor. In particular, TGF-β signaling plays an important role during metastasis of breast cancer. Recently, epithelial-mesenchymal transition (EMT) has been shown to confer malignant properties such as cell motility and invasiveness to cancer cells and plays crucial roles during cancer metastasis. Moreover, breast stem-like cells exhibit EMT properties. Because TGF-β is a potent regulator of EMT as well as cell stemness, TGF-β signaling might play a crucial role in the regulation of breast cancer stem cells. [ABSTRACT FROM AUTHOR]

Radio occultation observations of the electron density near the lunar surface were conducted during the SELENE (Kaguya) mission using the Vstar and Rstar sub-satellites. Previous radio occultation measurements conducted in the Soviet lunar missions have indicated the existence of an ionosphere with peak densities of several hundreds of electrons per cubic centimeters above the dayside lunar surface. These densities are difficult to explain theoretically when the removal of plasma by the solar wind is considered, and thus the generation mechanism of the lunar ionosphere is a major issue, with even the validity of previous observations still under debate. The most serious error source in the measurement is the fluctuation of the terrestrial ionosphere which also exists along the ray path. To cope with this difficulty, about 400 observations were conducted using Vstar to enable statistical analysis of the weak signal of the lunar ionosphere. Another method is to utilize Vstar and Rstar with the second one being used to measure the terrestrial ionosphere contribution. The observations will establish the morphology of the lunar ionosphere and will reveal its relationship with various conditions to provide possible clues to the mechanism. [ABSTRACT FROM AUTHOR]

The article presents a research which highlights the effect of image degradations with sensor technology based on scattered-light detection. It mentions that the study used a simulated smeared finger, where in the researchers printed a small black dots on a transparent sheet and inserted between a finger and the sensor. The results shows that the rate of successful identification decreased constantly as the number of black dots increases.

Smad7 negatively regulates transforming growth factor (TGF)-ßsuperfamily signaling by binding to activated type I receptors, thereby preventing the phosphorylation of receptor-regulated Smads (R-Smads), as well as by recruiting HECT-type E3 ubiquitin ligases to degrade type I receptors through a ubiquitin-dependent mechanism. To elucidate the regulatory mechanisms of TGF-ßsignaling, we searched for novel members of proteins that interact with Smad7 using a yeast two-hybrid system. One of the proteins identified was the WW domain-containing protein 1 (WWP1) that is structurally related to Smad ubiquitin regulatory factors (Smurfs), E3 ubiquitin ligases for Smads and TGF-ßsuperfamily receptors. Using a TGF-ß-responsive reporter in mammalian cells, we found that WWP1 inhibited transcriptional activities induced by TGF-ß. Similar to Smurfs, WWP1 associated with Smad7 and induced its nuclear export, and enhanced binding of Smad7 to TGF-ßtype I receptor to cause ubiquitination and degradation of the receptor. Consistent with these results, WWP1 inhibited phosphorylation of Smad2 induced by TGF-ß. WWP1 thus negatively regulates TGF-ßsignaling in cooperation with Smad7. However, unlike Smurfs, WWP1 failed to ubiquitinate R-Smads and SnoN. Importantly, WWP1 and Smurfs were expressed in distinct patterns in human tissues and carcinoma cell lines, suggesting unique pathophysiological roles of WWP1 and Smurfs.Oncogene (2004) 23, 6914-6923. doi:10.1038/sj.onc.1207885 Published online 28 June 2004 [ABSTRACT FROM AUTHOR]

Runx proteins regulate various biological processes, including growth and differentiation of hematopoietic cells, lymphocytes, osteoblasts, and gastric epithelial cells. Some of the biological activities of Runx proteins are reminiscent of those of transforming growth factor (TGF)-β superfamily cytokines. Consistent with this notion, receptor-regulated Smads (R-Smads), signal mediators of the TGF-β superfamily cytokines, and Runx proteins have been shown to physically interact with each other. R-Smads activated by TGF-β and Runx proteins cooperatively induce synthesis of IgA in B lymphocytes, and those activated by bone morphogenetic proteins and Runx2 induce osteoblastic differentiation. Moreover, the R-Smad—Runx signaling pathways are regulated by an E3 ubiquitin ligase Smurf1, as well as a signal transducer of interferons, STAT1. Since Runxl and Runx3 are involved in the development of some cancers including acute leukemia and gastric cancer, it will be of interest to examine in detail whether TGF-β-specific R-Smads and Runx proteins coordinately regulate growth and differentiation of hematopoietic cells and gastric epithelial cells. [ABSTRACT FROM AUTHOR]

BMPs exert a negative growth effect on various types of cells. We have previously reported that BMP-2 inhibited the growth of HS-72 mouse hybridoma cells by inducing p21CIP1/WAF1 expression. In the present study, we demonstrated that BMP-2 activated the mouse p21CIP1/WAF1 promoter in HS-72 cells, and that a 29-base pair (b) region of the promoter (-1928/-1900 relative to the TATA box), conserved between mice and humans, was responsive to BMP-2 as well as expression of Smad1, Smad4, and constitutively active mutants of BMP type I receptors. Furthermore, an oligonucleotide containing the 29-b region was found to be associated with Smad4 and phosphorylated Smad1 in the nuclear extract of BMP-2-stimulated HS-72 cells. These results suggested that BMP-2 might activate p21CIP1/WAF1 transcription by inducing a binding of Smad4 and Smad1 to the 29-b region in HS-72 cells. Oncogene (2001) 20, 4383–4392. [ABSTRACT FROM AUTHOR]

Bone morphogenetic proteins (BMPs) are members of the TGF-β superfamily that play a pivotal role in bone formation during embryogenesis and fracture repair. BMP signaling occurs via hetero-oligomeric serine/threonine kinase complexes of BMP type I (BMPR-IA or BMPR-IB) and type II receptors (BMPR-II). BMPR-IA and IB are closely related receptors, with sequence differences conserved between different species, suggesting that they serve distinct functions. Here we report the cDNA cloning of human BMPR1B and the chromosomal localization of all three BMPR genes. Using somatic cell hybrid and FISH analyses, the BMPR1A, BMPR1B, and BMPR2 genes were assigned to 10q23, 4q22-24, and 2q33-34, respectively. A processed BMPR1A pseudogene was mapped to 6q23. [ABSTRACT FROM AUTHOR]

Discusses research which isolated the SMAD protein Smad6 in a mouse. SMAD proteins signalling mediators of TGF-Beta superfamily; Explanation of roles of particular SMAD proteins; Differences of Smad6 from other SMAD proteins; Smad6 and phosphorylation of other SMAD proteins; Positive and negative signal regulation by SMAD proteins in TGF-Beta superfamily.